on genetic risk variants for nicotine dependence. Independent of rs16969968, noncoding CHRNA5 SNPs have been found to tag cis-expression quantitative trait loci (cis-eQTL) and cis-methylation QTL (cis-meQTL) variants that regulate CHRNA5 RNA expression (rs588765 [48] and rs880395 [49]) and DNA methylation (rs11636753 [50]), respectively, in postmortem human PFC. Consistent with these findings, mouse models have indicated that genetically altered CHRNA5 RNA expression profoundly influences behavioral traits characteristic of nicotine dependence [51–53].
